Staff at the State University of New York Health Science Center at Brooklyn propose to study key aspects of the acquisition of hepatitis C virus and virologic replication as measured in serum shortly after infection in a cohort of women most of whom, but not all, are infected with HIV. The source of patients for study will be the WIHS (Women's Interagency HIV Study) which has been funded by the NIH since 1994 to study the natural history of HIV infection in women. Over 2600 women from 5 separate sites around the United States have been enrolled in this study and are followed every 6 months. There is approximately one HIV-seronegative control patient enrolled for every 5 HIV- seropositive patients. Extensive batteries of demographic, behavioral, clinical and laboratory data are collected from each woman at each study visit. Serum, plasma, and other clinical specimens from each women at each study visit have been saved in a central repository. While up to 30 percent of study enrollees have HCV antibody at entry, pilot studies conducted within the WIHS cohort suggest that a number of at risk women may have acquired hepatitis C virus infection sometime during the course of the study. This project proposes to screen all enrollees HCV-seronegative at enrollment for HCV antibody at the time of their last study visit and then to serially work through a serum specimen for each study visit until a 6 month period during which HCV acquisition occurred can be determined. Factors related to acquisition will be examined. Virologic studies using bDNA and RNA-PCR will be conducted immediately preceding and 0-18 months after seroconversion to characterize viral kinetics. Correlation between these findings and other clinical factors will be sought. This project is important because it attempts to address in a straightforward manner aspects of HCV infection which are not well 1) early HCV in women is poorly characterized 2) early HCV infection in HIV infected individuals is poorly characterized 3) Routes of non-parenteral acquisition of HCV remain unclear 4) what impact if any does knowledge of HCV infection have on behaviors. The identification of a well characterized cohort of HCV infected individuals with a clear time frame of infection would be a novel and useful effort in understanding this disease.